Rice starch is a promising biomaterial for thin film development in buccal drug delivery, but the plasticisation and antiplasticisation phenomena from both plasticisers and drugs on the performance of rice starch films are not well understood. This study aims to elucidate the competing effects of sorbitol (plasticiser) and drug (antiplasticiser) on the physicochemical characteristics of rice starch films containing low paracetamol content. Rice starch films were prepared with different sorbitol (10, 20 and 30% w/w) and paracetamol contents (0, 1 and 2% w/w) using the film casting method and were characterised especially for drug release, swelling and mechanical properties. Sorbitol showed a typical plasticising effect on the control rice starch films by increasing film flexibility and by reducing swelling behaviour. The presence of drugs, however, modified both the mechanical and swelling properties by exerting an antiplasticisation effect. This antiplasticisation action was found to be significant at a low sorbitol level or a high drug content. FTIR investigations supported the antiplasticisation action of paracetamol through the disturbance of sorbitol-starch interactions. Despite this difference, an immediate drug release was generally obtained. This study highlights the interplay between plasticiser and drug in influencing the mechanical and swelling characteristics of rice starch films at varying concentrations.
The current pharmacotherapies for Alzheimer's disease (AD) demonstrate limited efficacy and are associated with various side effects, highlighting the need for novel therapeutic agents. Natural products, particularly from medicinal plants, have emerged as a significant source of potential neuroprotective compounds. In this context, Cissampelos capensis L.f., renowned for its medicinal properties, has recently yielded three new proaporphine alkaloids; cissamaline, cissamanine, and cissamdine. Despite their promising bioactive profiles, the biological targets of these alkaloids in the context of AD have remained unexplored. This study undertakes a comprehensive in silico examination of the binding affinity and molecular interactions of these alkaloids with human protein targets implicated in AD. The drug likeness and ADME analyses indicate favorable pharmacokinetic profiles for these compounds, suggesting their potential efficacy in targeting the central nervous system. Molecular docking studies indicate that cissamaline, cissamanine, and cissamdine interact with key AD-associated proteins. These interactions are comparable to, or in some aspects slightly less potent than, those observed with established AD drugs, highlighting their potential as novel therapeutic agents for Alzheimer's disease. Crucially, Density Functional Theory (DFT) calculations offer deep insights into the electronic and energetic characteristics of these alkaloids. These calculations reveal distinct electronic properties, with differences in total energy, binding energy, HOMO-LUMO gaps, dipole moments, and electrophilicity indices. Such variations suggest unique reactivity profiles and molecular stability, pertinent to their pharmacological potential. Moreover, Molecular Electrostatic Potential (MEP) analyses provide visual representations of the electrostatic characteristics of these alkaloids. The analyses highlight areas prone to electrophilic and nucleophilic attacks, indicating their potential for specific biochemical interactions. This combination of DFT and MEP results elucidates the intricate electronic, energetic, and electrostatic properties of these compounds, underpinning their promise as AD therapeutic agents. The in silico findings of this study shed light on the promising potential of cissamaline, cissamanine, and cissamdine as agents for AD treatment. However, further in vitro and in vivo studies are necessary to validate these theoretical predictions and to understand the precise mechanisms through which these alkaloids may exert their therapeutic effects.
The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.
Breast cancer remains a significant challenge in oncology, highlighting the need for alternative therapeutic strategies that target necroptosis to overcome resistance to conventional therapies. Recent investigations into natural compounds have identified 8,12-dimethoxysanguinarine (SG-A) from Eomecon chionantha as a potential necroptosis inducer. This study presents the first computational exploration of SG-A interactions with key necroptotic proteins-RIPK1, RIPK3, and MLKL-through molecular docking, molecular dynamics (MD), density functional theory (DFT), and molecular electrostatic potential (MEP) analyses. Molecular docking revealed that SG-A exhibited a stronger affinity for MLKL (-9.40 kcal/mol) compared to the co-crystallized ligand (-6.29 kcal/mol), while its affinity for RIPK1 (-6.37 kcal/mol) and RIPK3 (-7.01 kcal/mol) was lower. MD simulations further demonstrated the stability of SG-A within the MLKL site, with RMSD values stabilizing between 1.4 and 3.3 Å over 300 ns, indicating a consistent interaction pattern. RMSF analysis indicated the preservation of protein backbone flexibility, with average fluctuations under 1.7 Å. The radius of gyration (Rg) results indicated a consistent value of ~15.3 Å across systems, confirming the role of SG-A in maintaining protein integrity. Notably, SG-A maintains two critical H-bonds within the active site of MLKL, reinforcing the stability of the interaction. Principal component analysis (PCA) indicated a significant reduction in MLKL's conformational space upon SG-A binding, implying enhanced stabilization. Dynamic cross-correlation map (DCCM) analysis further revealed that SG-A induced highly correlated motions, reducing internal fluctuations within MLKL compared to the co-crystallized ligand. MM-PBSA revealed the enhanced binding efficacy of SG-A, with a significant binding free energy of -31.03 ± 0.16 kcal/mol against MLKL, surpassing that of the control (23.96 ± 0.11 kcal/mol). In addition, the individual residue contribution analysis highlighted key interactions, with ARG149 showing a significant contribution (-176.24 kcal/mol) in the MLKL-SG-A complex. DFT and MEP studies corroborated these findings, revealing that the electronic structure of SG-A is conducive to stable binding interactions, characterized by a narrow band gap (~0.16 units) and distinct electrostatic potential favourable for necroptosis induction. In conclusion, SG-A has emerged as a compelling inducer of necroptosis for breast cancer therapy, warranting further experimental validation to fully realize its therapeutic potential.
A new fusidic acid-loaded hydrogel film was prepared via the solvent casting technique using alginate and Aloe vera. The hydrogel films were optimized using different ratios of sodium alginate, Aloe vera, and glycerin. The films containing 10% glycerin (w/w of alginate) exhibited the best appearance. Incorporating Aloe vera influenced the thickness, swelling behavior, water vapor permeability, and drug release profile of the hydrogel films. Higher Aloe vera content resulted in thicker films (up to a certain ratio), increased swelling, reduced water vapor permeability, and a prolonged drug release of up to 93% over 12 h. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of key functional groups and the interaction between the hydrogel components. The study suggests that the combination of sodium alginate, Aloe vera, and glycerin can improve the mechanical properties and drug release profiles of hydrogel films, making them a promising option for enhanced topical drug delivery and wound healing applications.